A “mystery swine disease” appeared in the 1980s, and has been present ever since in the pig industry, causing important economical damage worldwide (Neumann et al., 2005). The causative agent, designated Porcine Reproductive and Respiratory Syndrome virus (PRRSV), was first isolated in the Netherlands in 1991 and shortly after in the USA. It is a small enveloped positive-stranded RNA virus that is classified in the order Nidovirales, family Arteriviridae, genus Arterivirus together with equine arteritis virus, lactate dehydrogenase-elevating virus and simian hemorrhagic fever virus based on similar morphology, genomic organization, replication strategy and protein composition. In addition, they share a very narrow host tropism and a marked tropism for cells of the monocyte-macrophage lineage (Plagemann & Moennig, 1992). More specifically, in vivo, PRRSV infects subpopulations of differentiated macrophages, with alveolar macrophages being major target cells, although in infected boars, testicular germ cells have also been shown to allow PRRSV replication (Sur et al., 1997).
PRRSV is recognized worldwide as the economically most important viral pig disease. The virus causes severe productive losses in sows and infection of young piglets is implicated in the porcine respiratory disease complex (Rossow, 1998). Current vaccination treatments are based on modified live virus (MLV) vaccines and killed virus (KV) vaccines, but neither of these methods is My satisfactory in the treatment of PRRSV. MLV induce an immune response that protects against homologous PRRSV infection, but they are not fully safe to use.
First, an MLV can spread in some cases via placenta and cause reproductive disorders in sows (Dewey et al., 1999). Second, the vaccine virus can be shed via semen and reduce semen quality after vaccination (Nielsen et al., 1997). Third, it is possible that the vaccine virus reverts to virulent virus (Nielsen et al., 1997). A final problem is that PRRSV is an RNA virus that shows a lot of genetic variation (Meng, 2000). As a consequence, MLV vaccines do not always sufficiently protect against virus strains that are genetically different from the vaccine virus strain (Meng, 2000).
Killed virus vaccines, a.k.a. inactivated virus vaccines, are safe and more easily adjust to circulating virus, but current vaccines on the market do not provide sufficient virological protection against PRRSV. Nilubol et al. (2004) examined the effect of a killed PRRSV vaccine. A first observation was that the magnitude and the duration of viremia were not different between vaccinated pigs and control pigs. A second observation was that the serum neutralization (SN) antibody titers of vaccinated pigs were higher than the control pigs.
The inefficiency of the present inactivated PRRSV vaccines is partially related to the fact that there is currently no quality control of the viral antigen after inactivation, as seen, for example, in the development of HIV and influenza vaccines. For inactivated PRRSV vaccines, the amount of antigen is tested, but not the capability of the antigen to induce the production of PRRSV-neutralizing antibodies. It was shown in earlier studies, that PRRSV-neutralizing antibodies block infection, by blocking the interaction with the PRRSV internalization receptor on the aforementioned target cells (Delputte et al., 2004). This suggests that neutralizing epitopes are probably located within viral ligands that are involved in this interaction. It is accordingly to be expected that inactivation procedures that only have an influence on the genome will be the most efficient methods to inactivate PRRSV while preserving the neutralizing epitopes and, therefore, will be the most appropriate methods for developing a killed PRRSV vaccine.